Twisted tango: brain tumor neurovascular interactions - PubMed (original) (raw)

Review

. 2011 Oct 26;14(11):1375-81.

doi: 10.1038/nn.2955.

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Review

Twisted tango: brain tumor neurovascular interactions

Anita B Hjelmeland et al. Nat Neurosci. 2011.

Abstract

The brain is a complicated organ with complexity derived from cellular and microenvironmental interactions. Similarly, brain tumor cells actively modify and are regulated by their microenvironment. Brain tumors are highly heterogeneous and frequently show a cellular hierarchy with self-renewing tumorigenic brain tumor stem cells (BTSCs) at the apex. Although BTSCs are distinct from neural stem cells, they share characteristics, including bidirectional interplay with supportive vasculature critical for maintenance of undifferentiated states and survival. BTSCs stimulate angiogenesis through growth factor secretion and are enriched in perivascular niches. Microenvironmental conditions, including hypoxia, drive expression of stem cell genes and proangiogenic factors, further linking cellular hierarchy regulation and instructive stromal elements. BTSCs may also directly contribute to tumor vasculature through plasticity toward an endothelial lineage. Interrogating the codependence of BTSCs and the perivascular niche may directly inform clinical approaches for brain tumor therapy through targeting of highly angiogenic and tumorigenic cellular subsets.

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Figures

Figure 1

Figure 1. Learning the Steps –Isolation and Characterization of Brain Tumor Stem Cells

Brain tumor stem cells (BTSCs) from malignant tumors (glioma, medulloblastoma, ependymoma) can be enriched based on cell surface expression using flow cytometry (markers including but not limited to CD133, A2B5, CD171 (L1CAM), CD15/SSEA1, CD49f (Integrin a6), CD44, and EGFR). Upon enrichment, hierarchy should be validated by functional assays of tumor propagation. BTSCs often have cellular phenotypes associated with the promotion of angiogenesis, therapeutic resistance, immune evasion, and niche interactions which are elevated in comparison to non-stem tumor cells.

Figure 2

Figure 2. Shall we dance? Coordinated communication between cells in the perivascular niche

Neural stem cells (NSCs) present in the perivascular niche rely on a series of signals between the extracellular matrix (ECM), blood vessels (BV), ependymal cells (E), and other niche cells (NC) to promote their maintenance. Brain tumor stem cells (BTSCs) rely on similar interactions within the perivascular niche, which also consist of ECM, non-stem tumor cells (NSTC), and tumor blood vessels (TBV). BTSC plasticity towards an endothelial lineage and incorporation of these BTSCs derived endothelial cells (BDECs) into the vasculature may also contribute to the perivascular niche. Figure modified from Gilbertson & Rich.

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